2026-08-31 東京科学大学
図1. 本研究の概念図
＜関連情報＞
- https://www.isct.ac.jp/ja/news/ussy1b0lf9if
- https://pubs.acs.org/jacsat/article/148/32/34430/5242313/An-Adaptable-Porous-Metal-Organic-Framework-for
マイクログラムスケールでの「5の法則」を超える分子の構造可視化のための適応性多孔性金属有機構造体 An Adaptable Porous Metal–Organic Framework for Structural Visualization of Beyond Rule of 5 Molecules on the Microgram Scale
Taichi Baba;Yu Tagami;Natsumi Watanabe;Bun Chan;Tomoki Nakagawa;Yiying Zhu;Arihiro Iwasaki;Pavel M. Usov;Yuki Wada;Masaki Kawano
Journal of the American Chemical Society Published:August 04, 2026
DOI:https://doi.org/10.1021/jacs.6c08312
Abstract
Beyond rule of 5 (bRo5) pharmaceutical compounds represent major structural challenges due to their large size and complexity. Here, we show that a metal–organic framework, APF-40, enables encapsulation and structural visualization of bRo5 molecules. It comprises a new benzoate-substituted hexaazaphenalene ligand and Zn8 clusters forming a doubly interpenetrated framework. The dynamic movement of the two nets facilitates adaptive behavior, efficiently immobilizing molecules along with their solvation spheres. Structures of 12 guests, including eight bRo5 compounds with subtly differing substituent modifications─ methyl-to-ethyl, methoxy-to-hydroxy, and alkane-to-alkene─were precisely elucidated. Significantly, one compound, isolated from a commercially available sample, was identified as a novel ivermectin derivative. This work demonstrates μg-order structure determination of molecules larger than 500 Da, offering new possibilities for characterizing compounds previously intractable for established analytical techniques.
